In the industrial workplace the worker is exposed to hundreds of different organic chemicals, many of these of sufficiently toxic hazard that the levels of human exposure are closely regulated. Much less appreciated are the complex interactions arising from exposure to multiple agents. This is particularly true of the potential interaction of diverse toxic agents with ethanol, a widely used and often abused chemical agent, particularly among industrial workers. Perhaps this is best recognized in the interaction between ethanol (as well as other alcohols) and carbon tetrachloride. This has been shown to be due to an interaction of ethanol with the hepatic mixed fuction oxidase (MFO) system that activats (CC14 to its toxic form. Ethanol-induced induction of this system enhances the hepatotoxicity of cC14. In recent years carbon disulfide (CS2) has been shown to be shown to also be metabolized by the MFO system of liver to carbonyl sulfide (COS) and a reactive sulfur atom. Induction of the enzyme system leads to an enhanced elimination of CS2 as CO2 and thus, presumably, to a decreased neurotoxic hazard. But this occurs at the cost of increased hepatotoxicity due to the elevated liberation of the reactive sulfur. In this application we propose to study the effect of both acute and chronic ethanol (as well as several other alphatic alcohols such as methanol and 2-propanol) on the hepatic metabolism and toxicity of CS2. The kinetics of CS2 metabolism in isoated hepatic microsomes will be studied following in vivo and in vitro exposures to the alcohols. This will be done to determine if the alcohols can, under acute conditions, serve as alternate substrates for the MFO system and thus inhibit the metabolism of CS2, and under chronic conditions induce the enzyme system, thereby enhancing CS2 metabolism. These experiments will be substantiated by studying the effect of acute and chronic alcohol treatment on CS2 metabolism in vivo. The distribution of CS2 will be determined as will the exhalation of COS and CO2. Several indices of hepatic and neurotoxicity will also be evaluated. These include (1) liver histology for evidence of hepatic necrosis, (2) serum glutamic-pyruvic trnasaminase, (3) hepatic cytochrome P-450 levels, (4) hepatic P-450 dependent nitro-anisole demethylase and aniline hudroxylase and, (5) brain norepinephrine as a measure of neurochemical toxicity.